The present view of the neuroanatomy of the human visual system has been formulated from observations of gross pathological dissections, deductions made from clinical cases and inferences from animal studies. Further attempts to delineate the visual pathways in man have been limited by the infeasibility of contemporary neuroscience research methods for use in man. This has remained an obstacle in attempts to analyze the physiologic basis of human neuro-ophthalmic disease. We have recently developed and demonstrated the use of a staining method utilizing paraphenylene-diamine (PPD) to identify degenerated axons and axon preterminals in the human brain. The PPD method reliably stains degenerated axons even years after the neural lesion. Preliminary studies have been done on 19 post-mortem cases, 14 of these with documented optic nerve lesions. The primary visual pathways were studied with PPD conventional light microscopic methods, and EM. With this new method, degenerated retinofugal fibers and their terminals were followed to primary visual brain nuclei. Our studies confirm some previously proposed primary retinal projections, reveal neuroanatomical discrepancies between man and other species, and provide evidence for retinofugal pathways not previously described in man. The nature of the PPD stain and the long-term course of axonal degeneration will be studied by comparisons of PPD and EM in perfused experimental animal brains. With this new method, we can extend our preliminary findings by following degenerated axons and describing the terminal distribution patterns of the retinofugal fibers in human necropsy brain tissue in which previous damage to the visual system has occurred. We hope to identify other visual nuclei not previously demonstrated in man by examining brain areas suggested by experimental animal studies. It is also possible to identify various retinal fiber types by size, compare their distribution, and describe the post-synaptic changes which may follow chronic deafferentation of visual input. The ability to directly study the human visual pathways will enable us to go beyond our reliance on animal models of human visual neuroanatomy. This opportunity to learn of the human visual anatomy may lead to the appreciation of the anatomical substrates with which we can better understand neuro-ophthalmic abnormalities, such as amblyopia or cortical blindness.